Chronic Kidney Disease of Unknown Origin: A Mysterious Epidemic

Abstract

Amongst the many threats to health in our world, the most challenging ones are the ones with unknown causes. There is a mysterious epidemic of kidney disease called chronic kidney disease of unknown etiology (CKDu) that is occurring in many parts of the world. Unrelated to known risk factors such as diabetes and hypertension, CKDu mostly affects the young and middle-aged, with slight preponderance in males. It mostly occurs in people living in rural areas, especially working in agricultural jobs. Worldwide, the number of people with chronic kidney disease, and those who need dialysis and renal replacement, is increasing every year as compared to other chronic conditions like diabetes and AIDS. It's not just alarming but a great challenge to healthcare systems across the world, especially in resource-poor countries. CKDu has become a silent killer for most patients. The occurrence of end-stage renal disease (ESRD) in CKDu can be catastrophic for individuals, especially in countries with limited medical facilities, causing a significant socio-economic burden. Even within these economically developing nations, people affected by CKDu usually are from the most vulnerable and underserved populations. As a definitive etiology has not been postulated for CKDu to date, this comprehensive review was undertaken to throw light on the poorly understood epidemiologic risk factors and the course of the disease.

Keywords: balkan endemic nephropathy; chronic kidney disease (ckd); mesoamerican nephropathy; sri lanka nephropathy; tondaimandalam nephropathy; uddanam nephropathy; unknown etiology.

Figure 1. Pathogenesis of chronic kidney disease of unknown origin (CKDu)

RAAS: Renin-angiotensin-aldosterone system; CKD: Chronic kidney disease; NSAIDs: Nonsteroidal anti-inflammatory drugs

Figure 2. Pathogenesis of Aristolochic acid nephropathy (AAN)

AA: Aristolochic acid; AKI: Acute kidney injury; OAT: Organic anion transporter; CKD: Chronic kidney disease; PCT: Proximal convoluted tubule; ESRD: End-stage renal disease; TP53: Tumor protein P53

Figure 3. Pathogenesis of Mesoamerican Nephropathy (MeN)

CKD: Chronic kidney disease; NSAIDs: Non-steroidal anti-inflammatory drugs